SUMMARY Common variable immunodeficiency (CVID) is a very frequent but heterogeneous syndrome of antibody formation. The primary defect remains unknown, but many reports describe peripheral blood T lymphocyte dysfunctions in a substantial proportion of CVID patients, which may impair T–B cell collaboration. In order to investigate whether such putative defects were intrinsic to T cells or, rather, secondary to quantitative differences in T cell subset distribution, or to other described disorders, we have used Herpesvirus saimiri (HVS) for the targeted transformation of CVID CD4+ and CD8+ T cells and subsequent functional evaluation by flow cytometry of their capacity to generate cell surface (CD154, CD69) or soluble (IL‐2, TNF‐α, IFN‐γ) help after CD3 engagement. Unexpectedly, the results showed that 40 different CVID blood samples exposed to HVS gave rise with a significantly increased frequency to transformed CD4+ T cell lines, compared to 40 age‐matched controls (27%versus 3%, P≤ 0·00002) suggesting the existence of a CVID‐specific signalling difference which affects CD4+ cell transformation efficiency. The functional analysis of 10 CD4+ and 15 CD8+ pure transformed T cell lines from CVID patients did not reveal any statistically significant difference as compared to controls. However, half of the CD4+ transformed cell lines showed CD154 (but not CD69) induction (mean value of 46·8%) under the lower limit of the normal controls (mean value of 82·4%, P≤ 0·0001). Exactly the same five cell lines showed, in addition, a significantly low induction of IL‐2 (P≤ 0·04), but not of TNF‐α or IFN‐γ. None of these differences were observed in the remaining CD4+ cell lines or in any of the transformed CD8+ cell lines. We conclude that certain CVID patients show selective and intrinsic impairments for the generation of cell surface and soluble help by CD4+ T cells, which may be relevant for B lymphocyte function. The transformed T cell lines will be useful to establish the biochemical mechanisms responsible for the described impairments.

Cytolytic CD8+ T lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To generate a cellular tool to study the defects of this T cell subset in vitro, we have used Herpesvirus saimiri, a lymphotropic virus that transforms human T lymphocytes into extended growth and in addition, endows them with natural killer (NK) features. Transformed CHS CD8+ T cells were generated and characterized in comparison with healthy controls. The results showed that transformed CHS T cells maintained the defects described in primary CHS lymphocytes, such as giant secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin-mediated cytolytic activity [which, however, could be restored after extended culture in the presence of interleukin-2 (IL-2)]. Upon activation with phorbol ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL-mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L. Transformed (and primary) CHS T cells were otherwise normal for cytolysis-independent activation functions, such as proliferation, surface expression of several activation markers including major histocompatibility complex class II, and cytokine or surface activation-marker induction. Therefore, the CHS protein [CHS1/LYST (for lysosomal traffic regulator)] can be dispensable for certain NK and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems to be required for microvesicle secretion of CD95L. We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.

White spot disease (WSD), caused by the white spot syndrome virus, is currently one of the primary causes of mortality and economic losses in the shrimp farming industry worldwide. In Mexico, shrimp production is one of the most important primary activities generating an annual income of USD 711 million. However, WSD introduction in 1999 had a devastating impact for the Mexican shrimp industry. The aim of this study was to characterize the WSD spatio-temporal patterns and to identify the primary risk factors contributing to WSD occurrence from 2005 to 2011 in Sinaloa, Mexico. We used data collected by the 'Comité Estatal de Sanidad Acuícola de Sinaloa' from 2005 to 2011 regarding WSD outbreaks as well as environmental, production and husbandry factors at farm level. The spatio-temporal patterns of WSD were described using space-time scan statistics. The effect of 52 variables on the time to WSD outbreak occurrence was assessed using a multivariable Cox proportional hazards model. Results reveal that WSD risk and survival time were not homogeneously distributed as suggested by the significant clusters obtained using the space-time permutation model and the space-time exponential model, respectively. The Cox model revealed that the first production cycle [hazard ratio (HR) = 11.31], changes from 1 to 1.4°C of temperature oscillation caused by 'El Niño'/'La Niña' events (HR = 1.44) and high average daily growths (HR = 1.26) were significantly associated with lower survival (i.e. shorter time to WSD outbreak) on farm. Conversely, shrimp weight at the moment of the outbreak (HR = 0.159), changes from -0.9 to -0.5°C of temperature oscillation caused by 'El Niño'/'La Niña' events (HR = 0.540), high superficial water temperature during the pound stocking (HR = 0.823) and high (>100) number of days of culture (HR = 0.830) were factors associated with higher survival. Results are expected to inform the design of risk-based, intervention strategies to minimize the impact of WSD in Mexico.