B cell immunodeficiency fails to develop in CD4-deficient mice infected with BM5: murine AIDS as a multistep disease.
The immunodeficiency syndrome murine AIDS (MAIDS), caused by the BM5 retrovirus preparation, involves the activation, division, and subsequent anergy of the entire CD4(+) T cell population as well as extensive B cell hyperproliferation and hypergammaglobulinemia, resulting in splenomegaly and lymphadenopathy, followed many weeks later by death. The development of MAIDS requires CD4(+) T cells and MHC class II expression by the infected host, supporting a role for T-B interaction in disease development or progression. To explore this possibility, we examined development of MAIDS in mice deficient in CD4 (CD4 knockout), in which T-B interactions are compromised. We find that in CD4 knockout hosts, BM5 causes T cell immunodeficiency in the remaining T cells but has only a limited ability to induce B cell phenotypic changes, hyperproliferation, hypergammaglobulinemia, or splenomegaly. There is also delayed death of infected mice. This implies that CD4 dependent T-B interaction is needed to induce the B cell aspects of disease and supports a multistep mechanism of disease in which B cell changes follow and are caused by CD4(+) T cell effects.
Harris
D P
DP
The Trudeau Institute, Saranac Lake, NY 12983, USA.
Koch
S
S
Mullen
L M
LM
Swain
S L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D015704:CD4 Antigens / Q000235:genetics*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D018450:Disease Progression; D006942:Hypergammaglobulinemia / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000821:virology; D008206:Lymphatic Diseases / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D016131:Lymphocyte Subsets / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000821:virology; D012192:Retroviridae Infections / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
D015704:CD4 Antigens