EducationBSc - Linkoping University, Sweden, 1988 PhD - Uppsala University, Sweden, 1994PubMed articles
Our laboratory has a long-standing interest in comparative immunology and using the channel catfish as a model, we and our collaborators have previously demonstrated that catfish possess cytotoxic T lymphocytes (CTL) capable of killing allogenetic target cells. Such CTL have been successfully cloned and are maintained as long-term cell lines. These lines are granular, and express TCRa/b transcripts, as well as message for perforin and granzymes, indicating they are authentic CTL. In addition, it has been established that catfish have natural killer (NK) cells and that some of these express IgM binding receptors (FcRs), enabling them to kill targets by antibody-dependent cell-mediated cytotoxicity (ADCC). Efforts to identify this putative catfish FcRs among expressed sequence tags (ESTs) in the NCBI database yielded a unique soluble IgM binding FcR, termed IpFcRI. This is the first FcR described in a cold-blooded vertebrate, but is not the receptor expressed by catfish NK cells. Currently our research is focused on two interrelated projects with the goals to understand:
In the first project, we will, in collaboration with Drs. Wilson and Chinchar, identify and phenotypically characterize virus-specific CTL using the channel catfish virus (CCV; Ictalurid herpesvirus-1) as a model virus. CCV is a major pathogen of fingerling catfish with the potential to cause die-offs that kill up to 100% of infected fish. The possibility of serious economic loss among producers of fry and fingerlings, coupled with CCV’s potential as a vaccine vector, and its use as a model pathogen, support the need for research into the nature of the CCV-specific anti-viral response. CCV grows readily in several catfish cell lines including a clonal T cell line G14D and this, coupled with the availability of major histocompatibility complex (MHC) matched gynogenetic (double haploid) catfish provides us with an excellent model system for studying MHC restricted anti-viral immunity. It is anticipated that these studies will shed light on critical aspects of the catfish immune system and provide insights that can be exploited to protect this agriculturally important species from microbial pathogens. In the second project, we will identify FcRs and examine their downstream signaling events. Channel catfish express four different Ig light (L) chain isotypes: IgL F, IgL G, IgL sigma and IgL lambda. Because of isotypic exclusion, each catfish B cell will expresses only one of the IgL isotypes. However, a small cell population of 4-12% of catfish peripheral blood leukocytes (PBL) has been shown to express IgM together with both IgL F and IgL G chains and dual expression implies that these cells passively acquire serum IgM via a putative FcR. Importantly, these cells do not express mRNA for IgM and are capable of killing allogeneic cells, i.e. they have NK cell activity. In addition, we and our collaborators have shown that leukocyte immune-type receptors (IpLITR) are differentially expressed in catfish NK and CTL lines, and are preferentially upregulated in catfish PBL by in vitro allogeneic stimulation. This large, unique immune receptor family belongs to the Ig superfamily and is phylogentically related to members of both mammalian FcRs and proteins encoded within the leukocyte receptor complex, including some NK receptor. IpLITR are highly diverse, encoded on multiple chromosomes and comprise both inhibitory and activating forms. Currently little is known about their function, but we hypothesize that some IpLITR, recognize allogeneic ligands on target cells that serve as surrogates for altered self, and thus may play important inhibitory and stimulatory functions in fish cytotoxic cells and that others may function as Ig binding receptors.