Doctoral Dissertations

Date of Award

8-1991

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Biomedical Sciences

Major Professor

Raymond A. Popp

Committee Members

Frank Larimer, Wen Yang, Gene Rinchik

Abstract

Retroviruses are associated with a number of diseases in mice; lymphomas, leukemias and immunodeficiencies can result from retrovirus infections. The mouse strains C57BL/10 (B10) and C57BL/10.F-H-2n/n (B10.F) are congenic strains that differ only at the H-2 locus. They share a defective endogenous ecotropic retrovirus, emv-2, on chromosome 8. B10.F, however, also has an infectious ecotropic retrovirus called B10FV that is passed via maternal transmission. Few B10.F mice (<10%) die as a result of neoplastic diseases before 6 months of age. B10.F mice are deficient in cellular immune responses when compared to B10 mice. Responses to sheep red blood cells, T cell mitogens and B cell mitogens are lower in B10.F mice. FACS analysis of MoAB-treated B10.F spleen cells indicate a lower frequency of B cells and CD8+ T cells, but the CD4+ T cells frequency is unchanged in B10.F mice. A unique set of B cells that also carry T cell antigens on their surface, Ly-1 B cells, are increased in B10.F mice. To study whether the differences observed in B10.F mice are the result of the retrovirus infection or some H-2-linked gene(s), retrovirus-free H-2n/n mice (BXF2NN) mice were bred and infected with biologically cloned B10FV. BXF2NN mice infected with B10FV were anemic, with low hematocrits and abnormal RBC sizes. Infected BXF2NN mice likewise exhibited lower responses to T and B cell mitogens and to sheep red blood cells when compared to uninfected BXF2NN mice. The frequency of T cells, of both the CD4+ and CD8+ cell subsets, were reduced in infected BXF2NN mice, but the B cell frequency was unchanged in comparison to uninfected BXF2NN mice. The frequency of Ly1-B cells was also similar in the uninfected and infected BXF2NN mice, and was at levels equivalent to B10.F mice; this indicated that high Ly-1 B cell frequencies may be an H-2-related trait. Therefore, T and B cell responses, as well as CD4+ cell frequencies, are reduced in B10FV-infected mice. Also, important immune cell frequency differences exist between B10 (H-2b) and B10.F (H-2n) mice that must be considered when these strains are compared. Frequencies of B cells were lower in uninjected BXF2NN mice. The CD4 and CD8 T-cell subsets were significantly altered infrequency, with uninjected BXF2NN mice having a greater frequency of CD4+ T cells and a lower frequency of CD8+ T cells than B10 mice.

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