An early defect in primary and secondary T cell responses in asymptomatic cats during acute feline immunodeficiency virus (FIV) infection

Abstract

SUMMARYAs in HIV infection of humans, cats infected with FIV are particularly susceptible to secondary infection by opportunistic pathogens, suggesting an impaired ability to elicit an effective immune response against foreign antigens. In order to investigate the development of immunity in FIVinfected cats, we have used an autologous culture system to directly measure priming of naive CD4+ T eells to soluble protein antigen, in vitro. Using this assay, we showed previously that cats infeeted with FIV for several months had significantly reduced primary proliferative responses. We have now examined cats before infection, and at varying times after infection with FIV, to determine how soon after infeetion this defect in T eell priming was evident, compared with other quantitative and qualitative measurements of lymphocyte function. Our results showed a progressive decline in immune function in asymptomatic cats during the acute stage of infection with FIV. Primary T cell responses were most sensitive and a significant reduction in proliferation of naive T cells to foreign antigen occurred 5 weeks after infeetion, despite normal blastogenesis to T cell mitogens and normal CD4' /CDS * ratios at these times. Whilst lymphoeyte proliferation to T cell mitogens was unaffected throughout, a significant reduction in proliferation to a B cell mitogen occurred from week 8 onwards. CD4*/CD8' ratios fell signifieantly from week 13 onwards, and proliferation ofthe memory Tcell population to a recall antigen was significantly impaired later, from week 19 onwards. The defect in the priming of naive T cells to foreign antigen early after infection may be important in determining susceptibility to secondary infections.

Clinical Aspects of Feline Retroviruses: A Review

“…In addition, other immunologic abnormalities can be found. Lymphocytes may lose the ability to proliferate in response to stimulation with mitogens or antigens, and priming of lymphocytes by immunogens may be impaired [105,133,134,135,136,137,138,139]. Lymphocyte function may be reduced by altered expression of cell surface molecules, such as CD4, major histocompatibility complex II antigens, or cytokines and cytokine receptors [140,141,142,143,144], or through over-expression of abnormal molecules, such as receptors [145], leading to disrupted production of cytokines or receptor function.…”

Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (FIV)

“…As well as a quantitative decline in CD4 ' T lymphocytes in FIV infection, we have also shown an early qualitative defect in CD4 ' T cell ("unction in asymptomatic cats which precedes the loss of CD4' cells [5]. Our previous studies have demonstrated ihat in addition to depressed proliferation of metnory T celts to secondary recall antigen [6], primary proliferation of naive CD4' T ceils to foreign protein antigen is significantly impaired in infected cats [5.6].…”

“…Our previous studies have demonstrated ihat in addition to depressed proliferation of metnory T celts to secondary recall antigen [6], primary proliferation of naive CD4' T ceils to foreign protein antigen is significantly impaired in infected cats [5.6]. The defect in proliferation of the naive CD4' T cell subset precedes a ftinclioiial dclccl in memory CD4+ T cells [5]. Both the in vitro depletion and proliferative defects seen during FIV infection could be explained by the induction offCDinvilni.…”

“…palhogenie retroviral infection, occurring in its natural host. Our previous studies have shown that FIV-infected cats have qualitative defects in cellular immunity, including reduced secondary Tcell prolilerative responses loreeall antigens [5[ anti impaired proliferalion of naive CD4^ Tcells lo soluble foreign protein aniigen [5,6[. These defects in primary and secondary proiiferative T cell responses lo soluble antigen occur soon alter infeciion.…”

Interactions between bovine retroviruses and the host immune system

“…In infections with other lentiviruses such as HIV and FIV, it is well established that host immune functions are often suppressed prior to more obvious alterations in circulating lymphocyte numbers or development of clinical disease , Miedema et al, 1988, Bishop et al, 1992. Despite ongoing conjecture about the potential of BIV to cause immunosuppression In cattle (Brownlie et al, 1994), as well as the potential value of BIV as a model for other lentiviruses such as HIV, there have been few controlled studies of the effects of BIV infection on acquired immune responses.…”