Population Dynamics of CD4⁺ T Cells Lacking Thy‐1 in Murine Retrovirus‐Induced Immunodeficiency Syndrome (MAIDS)

Abstract

Increased numbers of CD4+ Thy‐1 cells have been described in the spleen (SP) of mice with retrovirusinduced immunodeliciency (MAIDS). Since this phenotypic abnormality might have considerable functional importance, the expansion of the CD4+ Thy‐1 subset in MAIDS was characterized further. CD4+ Thy‐1− and Thy‐1+ T‐cell is from infected mice expressed similar densities of CD3 and TCR γ/β. In contrast, the Thy‐I− subset was uniformly CD44hi, even early in the disease when part of Thy‐I+ cells were still CD4410. The emergence of CD4+ Thy‐1−cells occurred first in SP and lymph nodes and was observed later in thymus. The important fraction ofCD4+ cells lacking Thy‐1 normally present in Peyer's patches was only weakly modified. Despite the major expansion of the CD4+ Thy‐1− phenotype. the proliferating fraction was not higher in this subset than in CD4+ Thy‐1+ cells from infeeted miee. Persistence after hydroxyurea administration was identical in both subsets, indicating similar mean cell lifespans. Taken together, these results show that the major expansion of CD4+ Thy‐I− T‐cells in MAIDS is not ascribable solely to increased proliferation within this subset. Phenotypic analysis suggests that CD4+ Thy‐I− cells result from the differentiation of Thy‐I+ cells induced by activation signals related to retroviral infection.

Mice with Disrupted Type I Protein Kinase A Anchoring in T Cells Resist Retrovirus-Induced Immunodeficiency

“…A large proportion of CD4 + T cells is characterized by an unusual CD90.2 (Thy-1.2)-negative phenotype in LP-BM5-infected mice compared with uninfected controls (42,43) (Fig. 7A, middle and left panels).…”

Peyer's Patches in Murine AIDS: Dissociation Between Lymphoproliferation and Anergy

“…The role of the CD4 + Thy-1 ¹ phenotype is also intriguing. We have previously demonstrated that CD4 + Thy-1 ¹ T cells which expand in MAIDS originate from activated CD4 + Thy-1 + T cells rather than from the expansion of the CD4 + Thy-1 ¹ T cells from normal mice [7]. In addition, we have demonstrated impaired calcium fluxes in CD4 + Thy-1 ¹ T cells isolated from the LN of normal mice [31].…”

“…Using propidium iodide (PI) staining, we have previously compared the proliferating fraction of CD4 + T cells in PP versus LN during MAIDS [7]. Although higher than in the control mice, the proliferating fraction (S and G 2 + M) of CD4 + T cells was significantly lower in PP than in spleen or LN of the infected animals.…”

Increased cAMP levels and protein kinase (PKA) type I activation in CD4+ T cells and B cells contribute to the retrovirus‐induced immunodeficiency of mice (MAIDS). A useful in vivo model for drug testing in PKA type I‐ induced immunodeficiency

“…MAIDS is characterized by the dramatic expansion of a CD4 + T‐cell subset with an unusual CD90 ‐ phenotype (9, 10). In view of previous reports showing that CD4 + CD90 ‐ T cells play an important role in the pathogenesis of the syndrome (41), we measured cAMP levels in this subset and compared it with levels in the CD90 + counterpart (Fig.…”

“…In contrast to what is observed in the classical anergization models (engagement of the T‐cell receptor [TCR] in the absence of costimulation), exogenous interleukin 2 (IL‐2) fails to restore the proliferative responses of T cells from infected mice (8), suggesting the existence of a defect in the IL‐2 receptor signal transduction pathway. A large proportion of CD4 + T cells (but not CD8 + T cells) of infected mice are also characterized by an unusual CD90 (Thy‐1)‐negative phenotype (9, 10). It is unclear if the absence of membrane CD90 is due to a shedding process related to the cleavage of the glycosylphosphatidylinositol (GPI) anchor or if the protein is down‐regulated at the mRNA level.…”