Novel role of CD8(+) T cells and major histocompatibility complex class I genes in the generation of protective CD4(+) Th1 responses during retrovirus infection in mice.
CD4(+) Th1 responses to virus infections are often necessary for the development and maintenance of virus-specific CD8(+) T-cell responses. However, in the present study with Friend murine retrovirus (FV), the reverse was also found to be true. In the absence of a responder H-2(b) allele at major histocompatibility complex (MHC) class II loci, a single H-2D(b) MHC class I allele was sufficient for the development of a CD4(+) Th1 response to FV. This effect of H-2D(b) on CD4(+) T-cell responses was dependent on CD8(+) T cells, as demonstrated by depletion studies. A direct effect of CD8(+) T-cell help in the development of CD4(+) Th1 responses to FV was also shown in vaccine studies. Vaccination of nonresponder H-2(a/a) mice induced FV-specific responses of H-2D(d)-restricted CD8(+) cytotoxic T lymphocytes (CTL). Adoptive transfer of vaccine-primed CD8(+) T cells to naive H-2(a/a) mice prior to infection resulted in the generation of FV-specific CD4(+) Th1 responses. This novel helper effect of CD8(+) T cells could be an important mechanism in the development of CD4(+) Th1 responses following vaccinations that induce CD8(+) CTL responses. The ability of MHC class I genes to facilitate CD4(+) Th1 development could also be considerable evolutionary advantage by allowing a wider variety of MHC genotypes to generate protective immune responses against intracellular pathogens.
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Karin E
KE
Peterson
Ingunn
I
Stromnes
Ron
R
Messer
Kim
K
Hasenkrug
Bruce
B
Chesebro
D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005622:Friend murine leukemia virus / Q000472:pathogenicity*; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D020297:Mice, Congenic; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014412:Tumor Virus Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D006183:H-2 Antigens; D007371:Interferon-gamma